Composition, barrier film, and method for preventing contact dermatitis

ABSTRACT

The present invention relates to a composition, and a method for preventing or reducing contact dermatitis. The composition contains a polysaccharide; a low molecular weight, synergistic saccharide; a solvent; and optionally an additive material. 
     The present invention is further a dermatologically-compatible barrier film for preventing and reducing contact dermatitis which contains a polysaccharide; a low molecular weight, synergistic saccharide; and optionally one or more additives. The dermatologically-compatible barrier film is formed of a composition containing a polysaccharide; a low molecular weight, synergistic saccharide; a solvent; and optionally an additive material. The composition is a skin care product in a form of a lotion, a gel or a cream that is applied to skin of mammals. Once applied, the solvent in the composition evaporates, and thereby leaving behind a dermatologically-compatible barrier film containing a polysaccharide; a low molecular weight, synergistic saccharide; and optionally an additive material.

This application is a continuation-in-part of copending application Ser.No. 08/642,227, filed on Apr. 30, 1996. The present invention relates toa composition and a method for preventing or reducing contactdermatitis. A dermatologically-compatible barrier film for preventingcontact dermatitis is also included in the invention.

BACKGROUND OF THE INVENTION

Contact dermatitis is an inflammation of the skin and is an acute orchronic condition resulting from irritation by, or sensitization to,some substance in the environment. In mild cases, the symptoms areitching, burning, or reddening of the skin. In more severe cases,vesiculation and edema may be present and may be followed by weeping andcrusting. The most severe cases may be accompanied by bleeding vesiclesand gross edema.

Contact dermatitis is typically classified as primary irritantdermatitis or allergic contact dermatitis. Primary irritant dermatitisis the more common form of contact dermatitis. It is normally caused byirritating agents that will cause dermatitis in all persons uponsufficient exposure.

Allergic contact dermatitis may be caused by many substances whichinduce a reaction in some people upon physical contact. This reactionusually does not occur with the initial contact, but only uponsubsequent exposures. More specifically, this reaction creates ahypersensitive state in susceptible individuals. Thus, upon subsequentcontact, these individuals will develop contact dermatitis.

In view of the above, contact dermatitis is a serious concern to manypeople, including industrial workers. Therefore, the need for protectionagainst contact dermatitis is apparent, especially when occupationalallergic contact dermatitis can result in lost wages and discomfort toworkers.

Attempts have been made to inhibit and treat contact dermatitis. Forexample, U.S. Pat. No. 4,112,067 to Tomalia et al. disclose a method oftreating and controlling dermatitis in humans who have been exposed toallergens produced by plants of the genus Rhus. The method of Tomalia etal. requires topical application of a polyamine polymer having amolecular weight of at least 5000. This does not suggest the presentinvention.

U.S. Pat. No. 4,451,453 to Lay et al. also discloses a method ofcontrolling and treating dermatitis in humans who have been exposed toallergies produced by plants of the genus Rhus. The method of Lay et al.requires topical application of a cross-linked copolymer of isobornylacrylate, isobornyl methacrylate, styrene, or alkylstyrene and one ormore alkyl esters of a C₁ to C₂₀ alcohol and acrylic or methacrylicacid. This also does not suggest the present invention.

U.S. Pat. Nos. 3,961,044 and 3,981,990 to Kelly et al, and 4,137,301,4,141,966, 4,144,319 and 4,160,818 to Willer et al. disclosecompositions and methods for preventing or reducing irritation of theskin resulting from allergic contact dermatitis by applying a protectiveagent. The protective agent of Willer et al. is an organic compoundhaving at least two polar groups separated by a chain of at least 15carbons. However, these compositions and methods do not disclose orsuggest the use of a low molecular weight saccharide that enhances theprotection against contact dermatitis.

Accordingly, it is an object of the present invention to provide acomposition, a dermatologically-compatible barrier film, and a methodfor preventing or reducing contact dermatitis.

SUMMARY OF THE INVENTION

The present invention is a composition for preventing or reducingcontact dermatitis. The composition contains a polysaccharide; a lowmolecular weight, synergistic saccharide; a solvent; and optionally anadditive material. The composition of the present invention can alsoinclude an antimicrobial agent.

The polysaccharide of the present invention is preferably a cellulosederivative.

The low molecular weight, synergistic saccharide is preferably anunmodified monosaccharide, a derivatized monosaccharide, an unmodifieddisaccharide, a derivatized disaccharide, a hydrolyzed starch, or aderivatized starch hydrolysate.

The solvent is preferably water, lower alcohol, low molecular weightglycol, or mixtures of these.

The additives include any physiologically-psychologically beneficialingredients that are chemically compatible with the present compositionand do not interfere with barrier performance.

The present invention is also a method for preventing and reducingcontact dermatitis by applying the above described composition to skinof mammals in an amount effective to prevent contact dermatitis.

The present invention is also a dermatologically-compatible barrier filmfor preventing or reducing contact dermatitis. Thedermatologically-compatible barrier film is formed from a compositioncontaining polysaccharide; a low molecular weight, synergisticsaccharide; a solvent; and optionally an additive material.

In a preferred embodiment, the invention includes adermatologically-compatible, barrier film composition which comprises ahydrophilic, nonionic, film-forming polysaccharide and a barrier filmenhancer which by itself has little or no barrier properties and whichis comprised of unmodified or derivatized monosaccharides, disaccharidesand/or hydrolyzed starch. When dissolved in adermatologically-compatible solvent and applied to skin, the compositiondries to a non-sticky film which reduces or inhibits penetration bynatural or synthetic allergenic agents or other skin irritants.

The advantages achieved by the present invention include the use of thelow molecular weight, synergistic saccharide to produce a more effectivedermatologically-compatible barrier film, which in turn, provides a moreeffective prevention of contact dermatitis.

In addition, the advantages achieved by the present invention alsoinclude the use of antimicrobial agent in the composition to (1) enhancethe preservation of the composition; (2) prevent or reduce infection ofopen or infected skin when applying the composition; and (3) cleanseskin prior to forming an invisible glove for preventing and reducingcontact dermatitis.

DETAILED DESCRIPTION OF THE INVENTION

Contact dermatitis can be caused by a variety of irritants. The mostwidely known natural allergens which are capable of sensitizing andcausing contact dermatitis in many people are antigenic plants of thegenus Rhus, such as poison ivy, poison oak, and poison sumac.

Other widely known allergens are commercial products such asinsecticides containing Pyrethrum or Rotenone, dye intermediates such asaniline, nitro compounds, anthracene, and derivatives thereof, dyes suchas paraphenylenediamine and aniline black, photo developers such ashydroquinone and para-amido-phenol, antioxidants such as hexamethylenetetramine, and synthetic and natural resins such as wood rosin andphenol formaldehyde, and detergents and constituents of rubber and latexgloves.

The present invention relates to a composition for preventing orreducing contact dermatitis which includes a polysaccharide; a lowmolecular weight, synergistic saccharide; a solvent; and optionally anadditive material. The composition can also include an antimicrobialagent.

The present invention also involves the application of adermatologically-compatible barrier film to the skin prior to contactwith agents capable of causing allergic contact dermatitis (e.g., plantsof the genus Rhus, insecticides, dyes and dye intermediates, etc.) toeliminate or lessen the dermatological reaction.

The dermatologically-compatible barrier film includes a polysaccharideand a low molecular weight, synergistic saccharide. More specifically,the dermatologically-compatible barrier film is derived from acomposition containing a polysaccharide; a low molecular weight,synergistic saccharide; a solvent; and optionally an additive material.The dermatologically-compatible barrier film can also be derived from acomposition containing a polysaccharide; a low molecular weight,synergistic saccharide; an antimicrobial agent; a solvent; andoptionally an additive material.

The composition, in the form of a lotion or a cream, is then applied toskin. Once applied to the skin, the solvent in the compositionevaporates, and thereby leaving behind a film containing apolysaccharide; a low molecular weight, synergistic saccharide; andoptionally an additive material. The film left behind can also contain apolysaccharide; a low molecular weight, synergistic saccharide; anantimicrobial agent; and optionally an additive material.

The polysaccharide of the present invention is compatible with skin,soluble in solvents, and a good film--former. Preferably, it is acellulose derivative. The polysaccharides include alkyl derivativesand/or hydroxyalkyl derivatives of cellulose, such as methylcellulose,ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,hydroxybutylcellulose, methylhydroxyethylcellulose,methylhydroxypropylcellulose, methylhydroxybutylcellulose,hydroxyethylhydroxypropylcellulose, and ethylhydroxyethylcellulose. Morepreferably, the polysaccharide is a hydroxypropylcellulose. The degreeof polymerization (DP) of the polysaccharide is not critical, but,should be high enough to provide good film-forming properties yet lowenough to provide flowable solutions which are easily applied to skin.The cellulose derivatives of the present invention are preferablynonionic, linear, polysaccharides. The polysaccharides can be chemicallymodified by methods known in the art to render them soluble in water oralcohol.

The percentage of the polysaccharide in the composition is about 5 wt. %to about 20 wt. %, and preferably, about 15 wt. %.

Low molecular weight, synergistic saccharides used in the invention arecomprised of a relatively small number of monosaccharide units ascompared with the polysaccharide of the invention. Low molecular weight,synergistic saccharides can be unmodified or derivatizedmonosaccharides, disaccharides, or hydrolyzed starches which arepreferably polar and hydrophilic. Synergistic means that the protectiveproperties of the composition of the invention are greatly enhanced bythe presence of the low molecular weight, saccharides which bythemselves possess little or no barrier properties.

The low molecular weight, synergistic saccharides of the presentinvention include an unmodified monosaccharide, a derivatizedmonosaccharide, an unmodified disaccharide, a derivatized disaccharide,a hydrolyzed starch, or a derivatized starch hydrolysate. Themonosaccharide contains 5 or 6 carbons. Disaccharides contain twosaccharide units. Derivatized monosaccharides, disaccharides, and starchhydrolysates refer to monosaccharides, disaccharides, and starchhydrolysates that have been produced from other compounds, e.g., in amanner known in the art, preferably by alkoxylation, hydroxyalkylation,or esterification with fatty esters. Hydrolyzed starches includestarches that have been modified, e.g., in a manner known in the art.

Some examples of the unmodified monosaccharide are fructose, glucose,and mannose.

Some examples of the unmodified disaccharide are sucrose and maltose.

Some examples of a derivatized monosaccharide are ethoxylates of methylglucoside, propoxylates of methyl glucoside, propoxylates of methylglucoside distearate, and methyl glucose dioleate. Preferably, thederivatized monosaccharide is Methyl Gluceth-10 (10 mole ethoxylate ofmethyl glucoside), Methyl Gluceth-20 (20 mole ethoxylate of methylglucoside), PPG-10 Methyl Glucose Ether (10 mole propoxylate of methylglucoside), PPG-20 Methyl Glucose Ether (20 mole propoxylate of methylglucoside, PPG-20 Methyl Glucose Ether Distearate (20 mole propoxylateof methyl glucoside distearate) or methyl glucose dioleate. The names ofthe examples of the derivatized monosaccharides described above arestandard names of the Cosmetic, Toiletries & Fragrance Association(CTFA). Amerchol Corp., Amerchol The Elegance Engineer, (September1992).

Dextrose Equivalence (DE) is a well known unit of measurement in thestarch industry. It is the inverse of the degree of polymerization (DP)and the quantitative measurement of starch polymer hydrolysis. Forexample, the total hydrolysis that starch can convert to dextrose(glucose) is 100%. Thus, the DE of glucose is 100. The DE of thehydrolyzed starch to be used in the present invention is at least about4, preferably about 6 to about 100.

Some examples of the derivatized disaccharide and derivatized starchhydrolysate are ethoxylates and propoxylates, such as about 10 moleethoxylates, about 20 mole ethoxylates, about 10 mole propoxylates, andabout 20 mole propoxylates.

Some examples of a hydrolyzed starch are maltodextrin and corn syrupsolids. Preferably, the DP of the maltodextrin is from about 1 to about19 and the DP of corn syrup solids is from about 20 to about 100.

Preferably, the low molecular weight, synergistic saccharide is aderivatized monosaccharide; more preferably, the low molecular weight,synergistic saccharide is Methyl Gluceth-20 (20 mole ethoxylate ofmethyl glucoside).

The percentage of the low molecular weight, synergistic saccharide inthe composition is about 2 wt. % to about 10 wt. %, and preferably,about 5 wt. %.

Antimicrobial agents that can be used in the present invention arecompatible with skin and soluble in solvents. In addition, antimicrobialagents are active against a broad spectrum of microorganisms, includingbut are not limited to, gram positive and gram negative bacteria, yeast,and mold. Examples of the antimicrobial agents include, but are notlimited to, triclosan (5-chloro-2-(2,4-dichlorophenoxy) phenol which isalso known as Irgasan™ DP 300 manufactured by Ciba-Geigy Corporation),hexetidine (5-amino-1,3-bis(2-ethylhexyl)-5-methyl-hexahydropyrimidine),chlorhexidine salts (salts ofN,N``-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,14-tetraazatetradecanediimidiamide),2-bromo-2-nitropropane-1,3-diol, hexyresorcinol, benzalkonium chloride,cetylpyridinium chloride, alkylbenzyldimethylammonium chlorides, iodine,phenol derivatives, povidone-iodine (polyvinylpyrrolidinone-iodine),parabens, hydantoins (2,4-imidazolidinedione), hydantoins derivatives(derivatives of 2,4-imidazolidinedione), phenoxyethanol, cis isomer of1-(3-chloroallyl)-3,5,6-triaza-1-azoniaadamantane chloride(quarternium-15 which is also known as Dowicil 200 manufactured by DowChemical Company), diazolidinyl urea, benzethonium chloride,methylbenzethonium chloride, and mixtures thereof. Examples ofhyndantoin derivatives include, but are not limited to,dimethylol-5,5-dimethylhydantoin (glydant). Preferably, examples of theantimicrobial agents include triclosan, cis isomer of1-(3-clhoroallyl)-3,5,6-triaza-1-azoniaadamantane chloride(quarternium-15), hyndantoins, hyndantoin derivatives such asdimethylol-5,5-dimethylhydantoin (glydant), and mixtures thereof.

The percentage of the antimicrobial agents in the composition is about0.01 wt. % to about 10 wt. %, and preferably, about 0.01 wt. % to about2 wt. %.

Solvents to be used in the invention are preferably compatible withskin, capable of drying in a reasonable amount of time, and capable ofdissolving the solid ingredients of the composition.

The solvent of the present invention includes water, lower alcohols, lowmolecular weight glycols, or mixtures of these. Lower alcohols refer toC₁ to C₄ alcohols. Some examples of the lower alcohol are methanol,ethanol, 1-propanol, 2-propanol, and butanol. Some examples of the lowmolecular weight glycols are glycerol and propylene glycol. Preferably,the solvent is water, lower alcohol, low molecular weight, glycol, ormixtures thereof The solvent of the invention can be chosen to have theability to penetrate into the skin.

The percentage of the solvent in the composition is about 70 wt. % toabout 93 wt. %, and preferably, about 80 wt. %.

The additive material includes any physiologically-psychologicallybeneficial ingredients compatible with the composition of the presentinvention. Known physiologically-psychologically beneficial additivematerials include colorants, fragrances, sunscreen, insect repellants,surfactants (wetting agents), flow modifiers (rheology modifiers),cleansers, moisturizers, film solubility modifiers, film plasticizers,salts, natural extracts, and mixtures thereof that do not interfere withbarrier performance. In addition, the additive agent also includesexfoliants, astringents, antioxidants, vitamins, self-tanning gents,emulsifiers, emollients, enzymes, keratolytics, antipruritics,analgesics, anesthetics, antihistamines, antimicrobials, preservatives,antibiotics, antiseptics, antifungals, antivirals, other biologicallyactive agents, and mixtures that do not interfere with barrierperformance.

The percentage of the additive material in the composition is about 0.01wt. % to about 30 wt. %, and preferably, about 1 wt. % to about 20 wt.%.

The composition of the present invention can be formulated into skincare products, such as cosmetics and moisturizers in the form of alotion, a gel, or cream. The preferred embodiment may be considered apre-exposure lotion which protects the skin against allergens such aspoison ivy, oak, sumac, and other irritants.

The present invention is also a method for preventing or reducingcontact dermatitis by applying to skin of mammals adermatitis-preventing effective amount of a composition containing apolysaccharide; a low molecular weight, synergistic saccharide; asolvent; and optionally an additive material. The method of the presentinvention can also include applying to skin of mammals adermatitis-preventing effective amount of a composition containing apolysaccharide; a low molecular weight, synergistic saccharide; anantimicrobial agent; a solvent; and optionally an additive material.

The present invention is further a dermatologically-compatible barrierfilm for preventing or reducing contact dermatitis. Thedermatologically-compatible barrier film is formed of a compositioncontaining a polysaccharide; a low molecular weight, synergisticsaccharide; a solvent; and optionally an additive material. Thedermatologically-compatible barrier film can also be formed of acomposition containing a polysaccharide; a low molecular weight,synergistic saccharide; an antimicrobial; a solvent; and optionally anadditive material. The composition is a skin care product in a form of alotion, a gel, or a cream that is applied to skin of mammals. Onceapplied, the solvent in the composition evaporates, and thereby leavingbehind a dermatologically-barrier film containing polysaccharide; lowmolecular weight, synergistic saccharide; and optionally an additivematerial. The film left behind can also contain a polysaccharide; a lowmolecular weight, synergistic saccharide; an antimicrobial agent; andoptionally an additive agent.

The composition of the dermatologically-barrier film is about 14 wt. %to about 87 wt. % of the polysaccharide; about 5 wt. % to about 63 wt. %of the low molecular weight, synergistic saccharide; and optionallyabout 3 wt. % to 74 wt. % of the additive agent. The composition of thedermatologically-barrier film is about 14 wt. % to about 87 wt. % of thepolysaccharide; about 5 wt. % to about 63 wt. % of the low molecularweight, synergistic saccharide; about 0.1 wt. % to 60 wt. % of theantimicrobial agent, and optionally about 3 wt. % to 74 wt. % of theadditives.

The dermatologically-barrier film is a non-sticky film that can reduceor inhibit penetration by natural or synthetic allergenic agents orother skin irritants, including non-oily materials such as detergentsand constituents of rubber compounds. Advantageously, the film isnon-occlusive, non-toxic and flexible. The films are also colorlessalthough colorants can be added if desired. Moreover, the films canavoid powdering and flaking-off during use. The films are alsocosmetically acceptable and therefore amenable to formulation intoenvironmental protection skin care (facial) products as well as"invisible glove" products.

The dermatologically-compatible film of the present invention preferablyhas effective barrier properties. Advantageously, the polysaccharide inthe composition has hydrophilic, nonionic, film-forming properties, andsome barrier properties. In addition, although the low molecular weight,synergistic saccharide of the present invention by itself does not havefilm forming or barrier properties, when combined with the film formingpolysaccharide of the present invention, the combination produces a moreeffective film barrier than either component alone. The antimicrobialagent in the composition (1) enhance the preservation of thecomposition; (2) prevent or reduce infection of open or infected skinwhen applying the composition; and (3) cleanse skin prior to forming aninvisible glove for preventing and reducing contact dermatitis.

While it is not intended to be bound by any one theory, it is believedthat the short chains of sugar molecules of the low molecular weight,synergistic saccharide fill the voids in the film created by the muchlarger polysaccharide, and thereby providing a better film and moreeffective barrier.

EXAMPLES

The following examples have been set forth as a guide to thepractitioner, and are not meant in any way to limit the scope of thepresent invention. In the following examples, compositions were testedagainst the following four irritants:

1.3 wt. % pyrocatechol in glycerol

1.3 wt. % 1,4-phenylenediamine in glycerol

saturated benzyl disulfide in methanol solution

2.4 wt. % sodium lauryl sulfate in water

Film barrier performance of the compositions in the following exampleswas tested by the Attenuated Total Reflectance-Infrared (ATR-IR) method.In addition, the antimicrobial efficacy of the composition in thefollowing examples was tested by the U.S. Pharmacopeia NationalFormulary Procedures for Antimicrobial/Preservative Effectovemess andAntibiotics-Microbial Assay.

ATR-IR Method for Measurement of Film Barrier Performance

To a baseline-horizontal, zinc-selenium crystal of the Attenuated TotalReflectance attachment was placed a specific volume of the test solutionof the examples. After the solution air-dried to a film, a specificvolume of irritant was deposited on top of the dried film. The assemblywas placed in a Nicolet Impact Series 400D Fourier-Transform Infraredspectrometer equipped with a deuterated triglycine sulfate detector,Omnic software and operating at 4 cm⁻¹ resolution with Happ-Genzelapodization. Infrared spectra were obtained at 30 minute intervals.Selected absorbance bands were monitored for each spectra, depending onthe test irritant. These wavelengths were 1521 cm⁻¹ for pyrocatechol,1225 cm⁻¹ for sodium lauryl sulfate, 1515 cm⁻¹ for 1,4-phenylenediamine,and 1610 cm⁻¹ for benzyl disulfide.

The appearance of absorbance bands at the selected wavelengths resultfrom the permeation or penetration of irritant through the dry film. Thetime at which this occurs is a measure of the protection time period bythe barrier formulation being tested. A good correlation exists betweenthis data and clinical tests on humans.

U.S. Pharmacopeia National Formulary Procedures forAntemicrobial/Preservative Effectiveness

Twenty milliliters of the sample to be tested is transferred to asterile tube. The sample is inoculated with a suspension ofmicroorganisms in a ration of 0.1 mL to 20 mL of sample and mixed. Thesuspension of microorganisms consists of a mixture of gram positive andgram negative bacteria, yeast and mold. The inoculated tubes areincubated at 25° C. for periods of 7, 14, 21 and 28 days. The number ofviable organisms is determined at each time-period via plate count.Plate count involves pipetting an aliquot of the sample into a sterilepetri dish, adding an appropriate agar growth medium and incubating thepetri dish at 37° C. for 24 to 48 hours. The number of viable coloniesis then counted and recorded.

U.S. Pharmacopeia National Formulary Procedures forAntibiotics-Microbial

Sterile petri dishes containing an appropriate growth medium areprepared and seeded with select microoganisms. The film pellet isdeposited on the agar medium and the petri dish is incubated at 37° C.for 24 to 48 hours. The region of non-growth (the zone of inhibition) ismeasured and recorded.

COMPARATIVE EXAMPLES A TO N

Various compositions of the polysaccharide components and saccharidecomponents by themselves were prepared. The various compositions areshown in Table 1 as Comparative Examples A to N.

This composition was tested against pyrocatechol via the ATR-IR methodfor measurement of film barrier performance.

The film barrier performance was measured according to the ATR-IR methodabove using pyrocatechol irritant. 100 or 200 microliters of testsolution of the composition was tested against 20 microliters ofpyrocatechol irritant.

The results of the AIR-IR method are in Table 1.

                                      TABLE 1    __________________________________________________________________________    COMPARATIVE    CELLULOSIC COMPONENT    EXAMPLE NO.            Wt. %  Type Grade       Supplier                                           Wt. %    __________________________________________________________________________    A       0                              20    B       0                              20    C       0                              20    D       0                              15    E       0                              100    F       0                              100    G       0                              20    H       0                              20    I       0                              20    J       5      MC   Methocel A-15LV                                    Dow Chem                                            0    K       15     HEC  WP-09H      Union Carbide                                            0    L       15     HPC  KLUCEL EF   Aqualon                                            0    M       20     HPC  KLUCEL EF   Aqualon                                            0    N       5      HPMC Methocel K-100 LV                                    Dow Chem                                            0    __________________________________________________________________________            SACCHARIDE    COMPARATIVE            COMPONENT                SOLVENT                                           Break-through    EXAMPLE NO.            Type     Grade  Supplier                                 Wt. %                                     Type  Time (Hr.)    __________________________________________________________________________    A       d-fructose      Aldrich                                 80  Water 0    B       d-glucose       Aldrich                                 80  Water 0    C       d-sucrose       Aldrich                                 80  Water 0    D       maltodextrin    Grain Proc                                 85  Water 0    E       Methyl Gluceth-10                     Glucam E-10                            Amerchol                                  0        0.5    F       Methyl Gluceth-20                     Glucam E-20                            Amerchol                                  0        0.5    G       d-maltose       Aldrich                                 80  Water 0.5    H       d-mannose       Aldrich                                 80  Water 0    I       corn syrup solids                     Maltrin M-250                            Grain Proc                                 80  Water 0    J                            95  Water 1    K                            85  Water 2    L                            85  Ethanol                                           1    M                            80  Etbanol                                           2    N                            95  Water 0.5    __________________________________________________________________________     100 μl test solution was utilized in all Examples with exception of     Example J in which 200 μl test solution was utilized.

Example 1

Hydroxypropylcellulose (15 grams) (KLUCEL™ EF Grade, Hercules, Inc.) wassprinkled into 80 grams of denatured ethyl alcohol (SDA-40) and stirredat room temperature until fully dissolved. Methyl Gluceth-20 (5 grams)(Glucan™ E-20, Amerchol Corp.) was added and the mixture stirredbriefly.

This composition was evaluated by the ATR-IR method for barrierperformance against several skin irritants and by the clinical methodagainst Rhus extract.

The film barrier performance was measured according to the ATR-IR methoddescribed above using all four irritants. 200 microliters of testsolution of the composition was tested against 20 microliters of eachirritant.

The results of the ATR-IR method show that the above compositionprovides more than 8 hours of protection time for all irritants.

The clinical method against Rhus extract was performed as follows:

Forearms of five human subjects (known to be allergic to urushiol, theantigen in Rhus extract) were washed with soap and water andtowel-dried. Three test solutions of the above compositions were applied(about 0.2 ml each) to three designated 4×4 cm areas in the volar aspectof the subject's forearms. The fourth site was untreated and served asthe control.

Using a micropipette, 10 microliter of oleoresin extract standard (1:50dilution of Rhus oleoresin in ethanol) was applied to 0.6 cm diameterfilter paper discs. The discs were allowed to air-dry for 30 minutes andthen carefully applied with forceps to each test site. Semi-occlusivetape was placed over each disc. After 8 hours, the discs were removedand the forearms washed with warm water and soap and towel-dried.

The subjects returned to the clinic 72 hours (3 days) later and 120hours (5 days) for evaluation of dermatitis. This was performed in ablinded fashion using the following 5 point clinical scale:

    ______________________________________    Score         = 0    No Response. Normal skin condition.         = 1    Slight Response. Minimally elevated lesions and moderate                erythema.         = 2    Moderate Response. More elevated lesions with edema and                moderate erythema.         = 3    Strong Response. Uniformly raised lesions with intense                edema, erythema and crusting or scaling.         = 4    Very Strong Response. Vesicular reaction.    ______________________________________

The result of the clinical method showed that none of the five subjectsexhibited an inflammatory response 72 and 120 hours after contact withthe urushiol antigen. Positive level--2 inflammatory responses wereevident at the control sites (no barrier protection) of all fivesubjects.

Example 2

Hydroxypropylcellulose (15 grams) (KLUCEL™ EF Grade Hercules, Inc.) wassprinkled into 80 grams of distilled water and stirred at roomtemperature until fully dissolved. D-Fructose (Aldrich Chemical) (5grams) was added and the mixture stirred until homogenous.

This composition was tested against pyrocatechol via the ATR-IR methodfor measurement of film barrier performance.

The film barrier performance was measured according to the ATR-IR methodabove using pyrocatechol irritant. 100 microliters of test solution ofthe composition was tested against 20 microliters of pyrocatecholirritant.

The results of the ATR-IR method showed that the composition providedmore than 8 hours permeation or protection time.

Example 3

Hydroxyethylcellulose (15 grams) (CELLOSIZE™ Grade WP-09H, Union CarbideCorporation) was sprinkled into 80 grams of distilled water and stirredat room temperature until fully dissolved. Methyl Gluceth-20 (5 grams)(Glucam™ E-20Amerchol Corporation) was added and the mixture stirreduntil homogenous.

This composition was tested against pyrocatechol via the ATR-IR methodfor measurement of film barrier performance.

The film barrier performance was measured according to the ATR-IRmethod. 100 microliters of test solution of the composition was testedagainst 20 microliters of pyrocatechol irritant.

The results of the ATR-IR method shows that the composition provided 5hours permeation or protection time.

Examples 4 to 25

Various compositions of the cellulose and saccharide components of thepresent invention were prepared. The various compositions are shown inTables 2 and 3.

These compositions were tested against pyrocatechol via the ATR-IRmethod for measurement of film barrier performance.

The film barrier performance was measured according to the ATR-IRmethod. 100 or 200 microliters of test solution of the composition wastested against 20 microliters of pyrocatechol irritant.

The results of the ATR-IR method are shown in Tables 2 and 3.

                                      TABLE 2    __________________________________________________________________________                   CELLULOSIC COMPONENT    EXAMPLE NO.            Wt. %  Type Grade       Supplier                                           Wt. %    __________________________________________________________________________     4      15     HPC  KLUCEL EF   Aqualon                                           5     5      15     HPC  KLUCEL EF   Aqualon                                           5     6      15     HPC  KLUCEL EF   Aqualon                                           5     7      15     HPC  KLUCEL EF   Aqualon                                           5     8      15     HPC  KLUCEL EF   Aqualon                                           5     9      15     HPC  KLUCEL EF   Aqualon                                           5    10      15     HPC  KLUCEL EF   Aqualon                                           5    11      15     HPC  KLUCEL EF   Aqualon                                           5    12      15     HPC  KLUCEL EF   Aqualon                                           5    13      15     HPC  KLUCEL EF   Aqualon                                           5    14      15     HPC  KLUCELEF    Aqualon                                           5    15      15     HPC  KLUCEL EF   Aqualon                                           5    16      15     HPC  KLUCEL EF   Aqualon                                           5    17      15     HPC  KLUCEL EF   Aqualon                                           5    18      15     HPC  KLUCEL EF   Aqualon                                           5    __________________________________________________________________________            SACCHARIDE            COMPONENT                SOLVENT                                           Break-through    EXAMPLE NO.            Type     Grade  Supplier                                 Wt. %                                     Type  Time (Hr.)    __________________________________________________________________________     4      d-fructose      Aldrich                                 80  Water >8     5      d-glucose       Aldrich                                 80  Water 5     6      d-mannose       Aldrich                                 80  Water >8     7      d-sucrose       Aldrich                                 80  Water >8     8      d-maltose       Aldrich                                 80  Water 6            monohydrate     9      corn syrup solids                     Maltrin M-250                            Grain Proc                                 80  Water 5    10      maltodextrin                     Maltrin M-180                            Grain Proc                                 80  Water >8    11      PPG-10 MeGlu                     Glucam P-10                            Amerchol                                 80  Ethanol                                           5            ether    12      PPG-20 MeGlu                     Glucam P-20                            Amerchol                                 80  Ethanol                                           5.5            ether    13      MeGluceth-20                     Glucam E-20                            Amerchol                                 80  Ethanol                                           2            Distearate                     distear.    14      MeGlu Dioleate                     Grillocose DO                            RITA 80  Ethanol                                           4.5    15      MeGlu    Grillocose IS                            RITA 80  Ethanol                                           1            Sesquistearate    16      PPG-20 MeGlu                     Glucans P-20                            Amerchol                                 80  Ethanol                                           3            ether distearate                     distear.    17      sucrose shearate                     Grilloten                            RITA 80  Ethanol                                           0                     PSE 141G    18      Methyl Gluceth-20                     Glucam E-20                            Amerchol                                 40 + 40                                     Water +                                           5.5                                 Ethanol    __________________________________________________________________________     100 μl of test solution was utilized in all Examples

                                      TABLE 3    __________________________________________________________________________                   CELLULOSIC COMPONENT    EXAMPLE NO.            Wt. %  Type Grade       Supplier                                           Wt. %    __________________________________________________________________________    19       5     MC   Methocel A-15 LV                                    Dow Chem                                           5    20      15     EC   Ethocel     Dow Chem                                           5    21      15     HEC  WP-O9H      Union  5                                    Carbide    22      15     HPC  KLUCEL/EF   Aqualon                                           5    23      15     HPC  KLUCEL EF   Aqualon                                           5    24       5     HPMC Methocel K-100LV                                    Dow Chem                                           5    25      10     CMC  Cell Gum 7L2P                                    Aqualon                                           5    __________________________________________________________________________            SACCHARIDE            COMPONENT                SOLVENT                                           Break-through    EXAMPLE NO.            Type     Grade  Supplier                                 Wt. %                                     Type  Time (Hr.)    __________________________________________________________________________    19      Methyl Gluceth-20                     Glucam E-20                            Amerchol                                 90  Water 5    20      Methyl Gluceth-20                     Glucam E-20                            Amerchol                                 80  Ethanol                                           >8    21      Methyl Gluceth-20                     Glucam E-20                            Amerchol                                 80  Water 5    22      Methyl Gluceth-10                     Glucam E-10                            Amerchol                                 80  Ethanol                                           5    23      Methyl Gluceth-20                     Glucam E-20                            Amerchol                                 80  Ethanol                                           5    24      Methyl Gluceth-20                     Glucam E-20                            Amerchol                                 90  Water 1.5    25      Methyl Gluceth-20                     Methyl Amerchol                                 85  Water 0.5                     Gluceth-20    __________________________________________________________________________     100 μl of test solution was utilized in all Examples with exception of     Example 19 in which 200 μl test solution was utilized.

As demonstrated in Tables 2 and 3, the combination of a polysaccharide,i.e., a cellulose derivative, and a low molecular weight, synergisticsaccharide provides a dermatologically-compatible barrier film havingexcellent barrier properties. More specifically, Example 4 in Table 2shows that the combination of 15 wt. % HPC and 5 wt. % d-fructose in 80wt. % water provides more than 8 hours of protection time againstpyrocatechol irritant. In contrast, 15 wt. % HPC in 85 wt. % ethanolprovides only 1 hour of protection time (Comparative Example L in Table1). In addition, 20 wt. % d-fructose in 80 wt. % water does not provideany protection time whatsoever (Comparative Example A).

Similarly, Example 19 in Table 3 demonstrates that the combination of 5wt. % Methyl Cellulose (MC) and 5 wt. % Methyl Gluceth-20 in 90 wt. %water provides 5 hours of protection time. In contrast, 5 wt. % MC in 95wt. % of water only provides 1 hour of protection time (ComparativeExample J). In addition, 100 wt. % Methyl Gluceth-20 provides 0.5 hoursor less of protection time (Comparative Example F).

Furthermore, Example 21 in Table 3 shows that the combination of 15 wt.% HEC and 5 wt. % Methyl Gluceth-20 in 80 wt. % water provides 5 hoursof protection time against pyrocatechol irritant. In contrast, 15 wt. %HEC in 85 wt. % water provides only 2 hour of protection time(Comparative Example K in Table 1). In addition, 100 wt. % MethylGluceth-20 by itself provides 0.5 hour or less of protection time(Comparative Example F).

Tables 1 to 3 clearly demonstrate that the low molecular weight,synergistic saccharide of the present invention by itself hassubstantially no film-forming or barrier properties. However, when thelow molecular weight, synergistic saccharide is combined with thefilm-forming polysaccharide of the present invention, the combinationunexpectedly provides a more effective film barrier than eithercomponent alone.

Example 26

Hydroxypropylcellulose (30 grams) (KLUCEL™ EF Grade, Aqualon Company),Methyl Gluceth-20 (10 grams) (Glucamm™ E-20, Amerchol Corp.), andtriclosan (0.6 gram) (IRGASAN™ DP 300) and 159.4 grams SD Alcohol 40were mixed in a 250 ml NALGENE bottle to form a homogenous mixture.

Two hundred microliters of the formulation were dried to a film pelletat 80° C. in a draft oven for the Antibiotics-Microbial Assay inaccordance with the U.S. Pharmacopeia National Formulary Procedures. Theresults showed that the films tested exhibited activity against grampositive and gram negative bacteria and yeast.

For the ATR-IR test, 100 microliters of the formulation was depositedonto a ZnSe crystal and air-dried. The film barrier performance wasmeasured according to the ATR-IR method above using 20 microliters ofpyrocatechol irritant. The results of the ATR-IR method showed that thecomposition provided 5 hours permeation or protection time.

Example 27

Hydroxypropylcellulose (30 grams) (KLUCEL™ EF Grade, Aqualon Company),Methyl Gluceth-20 (10 grams) (Glucam™ E-20, Amerchol Corp.), and 0.2gram of DOWICIL™ 200 were mixed in distilled water (159.8 grams) to forma homogenous mixture.

The formulation was tested for antimicrobial/preservatives-effectivenessaccording to U.S. Pharmacopeia National Formulary Procedures against apool of microorganisms, including gram positive and gram negativebacteria, yeast and mold.

Twenty milliliters of the sample was inoculated with 0.1 ml of asuspension of microorganisms and incubated at 25° C. for 7, 14, 21, and28 days. Aliquots of the inoculated sample were plated out to determinethe number of viable organisms. The results showed that the formulationremained free of any detectable organisms following several cycles oftesting.

For the ATR-IR test, 100 microliters of the test solution of thecomposition were tested against 20 microliters of pyrocatechol irritantThe results of the ATR-IR method showed that the composition provided5.5 hours permeation or protection time.

While there have described what are believed to be the preferredembodiments of the invention, those skilled in the art will realize thatchanges and modification may be made thereto without departing from thespirit of the invention, and it is intended to claim all such changesand modifications are fall within the true scope of the invention.

What is claimed is:
 1. A composition for inhibiting or reducing contactdermatitis which comprises:(1) a polysaccharide, said polysaccharide isa nonionic cellulose derivative selected from the group consisting ofmethylcellulose, ethylcellulose, hydroxyethylcellulose,hydroxypropylcellulose, hydroxybutylcellulose,methylhydroxyethylcellulose, methylhydroxypropylcellulose,methylhydroxybutylcellulose, hydroxyethylhydroxypropylcellulose, andethylhydroxyethylcellulose; (2) a low molecular weight synergisticsaccharide, said low molecular weight, synergistic saccharide isselected from the group consisting of fructose, glucose, mannose,sucrose, maltose, maltodextrin, corn syrup solids, derivatizedmonosaccharide, derivatized disaccharide, and derivatized starchhydrolysate,said derivatized monosaccharide is selected from the groupconsisting of ethoxylates of methyl glucoside, propoxylates of methylglucoside, propoxylates of methyl glucoside distearate, and methylglucose dioleate, said derivatized disaccharide is selected from thegroup consisting of about 10 mole ethoxylates, about 20 moleethoxylates, about 10 mole propoxylates, about 20 mole propoxylates,said derivatized starch hydrolysate is selected from the groupconsisting of about 10 mole ethoxylates, about 20 mole ethoxylates,about 10 mole propoxylates, and about 20 mole propoxylates; (3) asolvent; and (4) an additive agent; said additive agent is selected fromthe group consisting of colorants, film solubility modifiers, filmplasticizers, salts, natural extracts, exfoliants, astringents,antioxidants, vitamins, self-tanning agents, emulsifiers, emollients,enzymes, keratolytics, antipruitics, analgesics, anesthetics,antihistamines, antimicrobial agents, preservaties, antibiotics,antiseptics, antifungals, antivirals, and mixtures thereof, and saidantimicrobial agent is selected from the group consisting of triclosan,hexetidine, chlorhexidine salts, 2-bromo-2-nitropropane-1,3-diol,hexyresorcinol, benzalkonium chloride, cetylpyridinium chloride,alklbenzlydimethylammonium chlorides, iodine, povidone-iodine, parabens,hydantoins, hydantoins derivaties, phenoxyethanol, cis isomer of1-(3-chloroallyl)-3,5,6-triaza-1-azoniaadamantane chloride, and mixturesthereof, wherein said polysaccharides is in the amount of about 5 wt. %to about 20 wt. %, wherein said low molecular weight, synergisticsaccharide is in the amount of 2 wt. % to 10 wt. %, wherein said solventis in the amount of about 70 wt. % to about 93 wt. %, and wherein saidadditive solvent is in the amount of about 0.01 wt. % to about 30 wt. %.2. The composition of claim 1, wherein said additive is an antimcrobialagent.
 3. The composition of claim 1, wherein said polysaccharide ishydroxypropylcellulose.
 4. The composition of claim 1, whereinderivatized monosaccharide is about 20 mole ethoxylate of methylglucoside.
 5. The composition of claim 1, wherein said solvent isselected from the group consisting of water, lower alcohols, lowmolecular weight glycols or mixtures thereof.
 6. The composition ofclaim 2, wherein said antimicrobial agent is selected from the groupconsisting of triclosan, cis isomer of1-(3-chloroallyl)-3,5,6-triaza-1-azoniaadamantane chloride, hydantoins,hydantoin derivatives, and mixtures thereof.
 7. The composition of claim2, wherein said polysaccharide is in the amount of about 5 wt. % toabout 20 wt. %, wherein said low molecular weight, synergisticsaccharide is in the amount of 2 wt. % to 10 wt. %, wherein saidantimicrobial agent is in the amount of about 0.1 wt. % to about 2 wt.%, wherein said solvent is in the amount of about 70 wt. % to about 93wt. %, and optionally wherein said additive is in the amount of about0.01 wt. % to about of 30 wt. %.
 8. A method for inhbiting or reducingcontact dermatitis which comprises:applying adermatologically-compatible barrier film composition to skin of mammals,wherein said composition comprises(1) a polysaccharide, saidpolysaccharide is a nonionic cellulose derivative selected from thegroup consisting of methylcellulose, ethylcellulose,hydroxyethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose,methylhydroxyetylcellulose, metylhydroxypropylcellulose,methylhydroxybutylcellulose, hydroxyethylhydroxypropylcellulose, andethylhydroxyethylcellulose; (2) a low molecular weight, synergiticsaccharide, said low molecular weight, synergistic saccharide isselected from the group consisting of fructose, glucose, mannose,sucrose, maltose, maltodextrin, corn syrup solids, derivatizedmonosaccharide, derivatized disaccharide, and derivatized starchhydrolysate, said derivatized mnonosaccharide is selected from the groupconsisting of ethoxylates of methyl glucoside, propoxylates of methylglucoside, propoxylates of methyl glucoside distearate, and methylglucose dioleate, said derivatized disaccharide is selected from thegroup consisting of about 10 mole ethoxylates, about 20 moleethoxylates, about 10 mole propoxylates, about 20 mole propoxylates,said derivatized starch hydrolysate is selected from the groupconsisting of about 10 mole ethoxylates, about 20 mole ethoxylates,about 10 mole propoxylates, and about 20 mole propoxylates; (3) asolvent; and (4) an additive agent, said additive agent is selected fromthe group consisting of colorants, fragrances, sunscreen, insectrepellants, surfactants, flow modifiers, agents, preservatives,antibiotics, antiseptics, antifungals, antivirals, and mixtures thereof,and said antimicrobial agent is selected from the group consisting oftriclosan, hexetidine, chlorhexidine salts,2-bromo-2-nitropropane-1,3-diol, hexyresorcinol, benzalkonium chloride,cetylpyridinium chloride, alklbenzlydimetlkylammonium chlorides, iodine,povidone-iodine, parabens, hydantoins, hydantoins derivatives,phenoxyethanol, cis isomer of1-(3-chloroallyl)3,5,6-triaza-1-azoniaadamantane chloride, diazolidinylurea, benzethonium chloride, methylbenzethonium chloride, and mixturesthereof, wherein said polysaccharide is in the amount of about 5 wt. %to about 20 wt. %, wherein said low molecular weight synergisticsaccharide is in the amount of 2 wt. % to 10 wt. %, wherein said solventis in the amount of about 70 wt. % to about 93 wt. %, and wherein saidadditive agent is in the amount of about 0.01 wt. % to about 30 wt. %.9. The method of claim 8 wherein said additive is an antimicrobialagent.
 10. The method of claim 8, wherein said polysaccharide ishydroxypropylcellulose.
 11. The method of claim 8, wherein derivatizedmonosaccharide is about 20 mole ethoxylate of methyl glucoside.
 12. Themethod of claim 8 wherein said solvent is selected from the groupconsisting of water, lower alcohols, low molecular weight glycols ormixtures thereof.
 13. The method of claim 9, wherein said antimicrobialagent is selected from the group consisting of triclosan, cis isomer of1-(3-chloroallyl)-3,5,6-triaza-1-azoniaadamantane chloride, hydantoins,hydantoin derivatives, and mixtures thereof.
 14. The method of claim 8,wherein said polysaccharide is in the amount of about 5 wt. % to about20 wt. %, wherein said low molecular weight, synergistic saccharide isin the amount of about 2 wt. % to about 10 wt. %, wherein saidantimicrobial agent is in the amount of about 0.1 wt. % to about 2 wt.%, wherein said solvent is in the amount of about 70 wt. % to about 93wt. %, and optionally wherein said additive agent is in the amount ofabout 0.01 wt. % to about of 30 wt. %.